Complex behaviors driven by remarkably simple genetics

A mouse's intricate architectural tastes are the product of "modular" genetics.

The simple entrance of this oldfield mouse burrow should not mislead you about its architectural complexity.

Vera Domingues/Hopi Hoekstra, Harvard University

Humans engage in a lot of complex behaviors, but many of them are learned. Genetics gives us a nervous system that's flexible enough to incorporate new behaviors, and we pick them up socially. But many animals display highly complex behavior that appears to be instinctual. Which raises the question of how these sorts of behaviors can be programmed into the nervous system genetically.

Pretty simply, if a new study of mice is to be believed. The work compared the architecture of burrows built by two closely related species. The researchers find the design of the animals' burrows is modular, and the two modules are largely controlled by a handful of genes—perhaps as few as four in total.

The work relied on two closely related species. One is the deer mouse, which is widespread in North America. This species makes very simple burrows, with a short entry passage leading to a nest. In the southeastern US, however, there's a closely related species, the oldfield mouse, that builds a far more complex home. This includes a much longer entrance passage and a secondary "escape tunnel" from the back of the nest that allows it a safe route out should a predator come in the front door.

Various information, such as the species' geographic ranges and their close similarity, suggest the oldfield mice are offshoots of the more widely ranging deer mouse. If accurate, this would suggest the oldfield's burrowing behavior evolved since its separation from the parent species.

To confirm the burrowing behavior was under genetic control, the authors brought some of each species into the lab and raised offspring in cages that lacked any material for them to dig burrows. Then, when the mice were mature, they were set loose into a larger area filled with a sandy soil. Despite never having seen a parent's burrow, the mice quickly dug one that was similar to those that their fellow species members dig in the wild. You can see an example of how the authors managed to study the burrow's properties in the video below.

The researchers obtained casts of the mice's burrows in order to measure them. (video courtesy of Jesse Weber, Harvard University)

With the importance of genetics established, the authors set about studying it. Because the two species are so closely related, they were able to get the mice to mate, creating an offspring that was a 50/50 mix of the DNA of the two species. They tested these hybrids for behavior, and in all cases, they acted like the oldfield mice, making longer burrows with an escape tunnel. That, in a classic Mendelian way, suggests the genes that control these behaviors are dominant.

At first glance, it also suggested the suite of behaviors might all be inherited together. But the authors did further crosses to test that by mating the hybrids with regular deer mice (which build simple burrows). The burrows made by the animals that resulted tended to be a bit shorter, on average, than those of the oldfield mice, and only some of these offspring made escape tunnels. The presence of an escape tunnel did not correlate with the length of the burrow, suggesting these two traits are unlinked.

To understand the inheritance better, the authors turned to DNA. Although the two species were still closely enough related that they could mate, they have been separated for long enough to pick up differences in their DNA that could be tracked using molecular tools. So the authors performed a type of analysis (termed quantitative trait locus mapping) to see which parts of the genome were associated with burrow length and the presence of an escape route.

They found three different regions in the genome that, combined, accounted for over half the genetic variation in the length of the burrow. Just one area of the genome seemed to be linked to the presence or absence of an escape route. Even the authors termed the number of sites involved "surprisingly small" (although each site could have more than one gene contributing to its impact).

They also note what appears to be a very complex series of differences is actually the product of both modular contributions (the contributions of genes to length and escape route) and additive (several sites contribute to generate the longer burrow length).

The obvious next step is to try to identify the actual genes involved. This won't necessarily be easy, in that the difference may involve changes in the regulation of a gene rather than the properties of the protein it encodes for, and these can be difficult to identify. Still, once that's done, we can start looking at what these genes actually do and where in the brain they're active. And that could give us the clearest picture yet of how complex instincts get wired into the brain.

This is amazing! In my opinion, I see this as being a landmark study if we can find the genes that underly the behavior. It's like looking at a huge application's source code that you didn't write and suddenly stumbling upon Sub Main()

Hey, John Timmer, is this the first study of it's kind to compare genetics with instinctual behavior? Has there been any work done like this on nest building? (How you can encode those behaviors in 'GTAC' always blew my mind)

I'd say if you think about it this almost has to be the case. Closely related species often behave in similar ways. Clearly if a large amount of difference in genetics were required in order to control this then it would be rather unlikely that A) complex behaviors would ever evolve at all or that B) they would prove to be so easily modified or elaborated.

One might well posit that taxa which evolve in the direction of 'evolvability' (which would include high level behavior and structure mediated by a few key genes) acquire greater fitness over geologic time. Imagine a 'mouse' in which every detail of the burrowing behavior is controlled by many genes which don't work under the control of a few moderators. Such mice would only function properly if all these genes worked correctly (compatibly at least) and it would be unlikely that such behavior could evolve in a coherent fashion. When compared to the actual mouse we see in reality this mouse would fair poorly over evolutionary time.

This is amazing! In my opinion, I see this as being a landmark study if we can find the genes that underly the behavior. It's like looking at a huge application's source code that you didn't write and suddenly stumbling upon Sub Main()

It's not Main() it's a couple bits buried within a huge binary. It's great, and it's a starting point but there remains a massive gulf between identifying these genes and understanding the mechanism by which they regulate really complex behavior (exit tunnel or not).

Hey, John Timmer, is this the first study of it's kind to compare genetics with instinctual behavior? Has there been any work done like this on nest building? (How you can encode those behaviors in 'GTAC' always blew my mind)

The authors say that most similar studies have looked at behaviors that will only take place in lab environments, and that this is one of the first to take a look at a behavior that's a clear replication of something that takes place in the wild and has been under natural selection.

There are many studies that perform similar work with morphology: the shape and location of body parts.

There's plenty of precedent for complex behaviours having a simple trigger; the parasite that makes an ant cling to the top of a blade of grass so that it can be eaten by a cow, and so go on to the next stage of its life-cycle, or another parasite that causes mice to hunt out the smell of cats rather than avoid it, for similar reasons, or Langton's Ant, where we actually know everything about the system but have no idea what's going on. Or any hormone or neurotransmitter, I suppose. These are just examples that occurred to me off the top of my head while I was reading the article.

It is terribly easy to over-interpret this data. Let us start by admitting we do not know "why" one species builds a burrow that has a particular average shape. It could well be the mouse equivalent of taste. One mouse might be more sensitive to body odors and prefers more ventilation. The value as an escape hatch could be an incidental benefit that became selected. Until proven, I do not believe that genes "code" for behaviors. Rather, behaviors emerge as a solution to certain drives. Similarly the hype about alcoholism, homosexuality, or even artistry and intelligence far overplays the concept of genetic hardwiring. Behavior does not reduce to base pairs despite the effort of some researchers to make it seem so.A plausible explanation could be that building an escape hatch is the rational product of feeling at risk. Slightly raising stress hormone levels could lead to that perception by one species of mouse. This in turn could be the indirect effect of metabolic or nutritional factors that no one would consider primary behavioral genes.

It is terribly easy to over-interpret this data. Let us start by admitting we do not know "why" one species builds a burrow that has a particular average shape. It could well be the mouse equivalent of taste.

Taste mapped pretty specifically to a small set of genetic traits that are different between the two related species, devoid of environmental cues or conditioning? Traits that are demonstrably heritable, and produce consistent behaviors when acted upon?

Quote:

Until proven, I do not believe that genes "code" for behaviors. Rather, behaviors emerge as a solution to certain drives.

I'm not sure what you think the overriding distinction is. If the mouse is burrowing a certain way because its genetic makeup predisposes it to feel "wrong" in a burrow that's too small or lacks an escape hatch, whether the cue it's acting upon is body odor or something else, how is that different? The genes are governing its behavior either way.

Quote:

Behavior does not reduce to base pairs despite the effort of some researchers to make it seem so.

This experiment is pretty compelling evidence that at least some behaviors do. And how else would you explain instinct, not just in these mice but also in other organisms like spiders, fish, birds, etc.?

The moment you begin arguing that human behavior is innate, you might as well give up on democracy and free will.

Which is not what we were talking about and is an Appeal to Consequence and Slippery Slope besides. You might want to read my post again, because I very nearly re-typed it word for word in response to this.

The moment you begin arguing that human behavior is innate, you might as well give up on democracy and free will.

*Some* human behaviors are innate. That is inarguable. When a baby feels discomfort, it cries. When your patellar ligament gets nudged, you kick.*Plenty* of animal behaviors are innate. Monarch butterflies fly to winter grounds last seen by their great-grandparents. Oldfield mice dig complex burrows without training.*None* of these behaviors preclude the existence of free will. If some portion of our hindbrain or amygdala contains hard wired instincts, so what? The human cerebrum is a vast self-modifying expanse with capabilities not found in other species.

The moment you begin arguing that human behavior is innate, you might as well give up on democracy and free will.

This just in: breathing is incompatible with free will and democracy.

To be fair, breathing isn't a behavior.

Something that I would consider an example of an "innate" human behavior is how children sexually segregate themselves during preadolescence. This behavior spans cultures, and isn't (necessarily) learned. And it's apparent purpose is to reduce sexual attraction to siblings or other close family members later on, IIRC.

Actually it is. It's a muscular action driven by the nervous system, meeting the needs of the organism, with multiple levels of control:- some purely automatic (timed cycles of bursting activity to drive "resting" breathing)- some stimulus-driven (blood levels of O2 and particularly CO2 are strong regulators)- some are unconscious parts of volitional behaviours (increase in respiration triggered by a startle, or the decision to run, or modulation of breathing cycles to suit speech)- some are deliberate control (when I decide to hold my breath). All these things interact with each other (e.g. rising CO2 will eventually override my decision to breath-hold, or speech patterns will be disrupted by the heavy breathing necessary after running). This multilevel, part automatic and part volitional control is part of EVERY movement and EVERY behaviour. When you walk, you merely select a target and a speed, and take note of the terrain in between. All the details are handled by complex pattern generators in the spinal cord, which handle a very wide range of surface conditions and stuff like muscle fatigue, without bothering the conscious mind. And yet we would very firmly regard walking as a willed behaviour.The point is that free will and intention can interact in very complex ways with control systems laid down by connections made in the embryo under strict genetic control. There is no sharp line between the lowest reflex and the highest volitional control - just a blend of influences. If you understand this, then genetic determinism coexists peacefully with the idea of free will.Where that will comes from, is a question beyond neuroscience's framework at present.

Incidentally, this should sound warning bells for anyone considering modifying genes in humans to "improve" humanity - behavioural changes resulting from such a thing could potentially eliminate what makes us "human."

(edited to add the following)

Quote:

Rather, behaviors emerge as a solution to certain drives.

What makes you so sure that it's an either/or proposition? What if it's a bi-directional process, whereby behaviours influence genes and genes influence behaviours? This would explain why genetic mutation occurs throughout populations - an individual tries a certain behaviour, if they perceive the result as successful they do more of it and it follows a path of, e.g. initial attempt -> conscious habit -> unconscious habit -> semi-autonomous response ("muscle memory") -> genetic trait. This would help explain the anomaly between the estimated number of random mutations that would have been needed for life as we know it to have developed on Earth and the average time between them given our current estimates of when life began: THE MUTATIONS ARE NOT RANDOM. Certain behaviours are much more likely given existing genetic traits, those behaviours lead to modified genetics which then influence the next generation(s). Edge cases of unlikely behaviours still occur; if the success of these is comparatively much, much better than the general population then it leads the evolution in a different direction - more successful for the species/genus concerned.

Incidentally, this should sound warning bells for anyone considering modifying genes in humans to "improve" humanity - behavioural changes resulting from such a thing could potentially eliminate what makes us "human."

(edited to add the following)

Quote:

Rather, behaviors emerge as a solution to certain drives.

What makes you so sure that it's an either/or proposition? What if it's a bi-directional process, whereby behaviours influence genes and genes influence behaviours? This would explain why genetic mutation occurs throughout populations - an individual tries a certain behaviour, if they perceive the result as successful they do more of it and it follows a path of, e.g. initial attempt -> conscious habit -> unconscious habit -> semi-autonomous response ("muscle memory") -> genetic trait. This would help explain the anomaly between the estimated number of random mutations that would have been needed for life as we know it to have developed on Earth and the average time between them given our current estimates of when life began: THE MUTATIONS ARE NOT RANDOM. Certain behaviours are much more likely given existing genetic traits, those behaviours lead to modified genetics which then influence the next generation(s). Edge cases of unlikely behaviours still occur; if the success of these is comparatively much, much better than the general population then it leads the evolution in a different direction - more successful for the species/genus concerned.

An obvious example of a behavior that selects itself is self-survival. This actually extends to kin-defense. If you or your close relatives do not survive, your genes are removed from the gene pool. The apparent result is affirmative selection of gene sets that "try" to avoid death. Suicidal behavior is an edge condition that is self correcting.

Of course free will is also involved, suicidal individuals can choose not to kill themselves & non-suicidals can choose to kill themselves for no apparent benefit. The "instinctive" behavior will make these aberrant behaviors the minority case for each set of "normal" behaviors.

This is amazing! In my opinion, I see this as being a landmark study if we can find the genes that underly the behavior. It's like looking at a huge application's source code that you didn't write and suddenly stumbling upon Sub Main()

Quote:

Hey, John Timmer, is this the first study of it's kind to compare genetics with instinctual behavior? Has there been any work done like this on nest building? (How you can encode those behaviors in 'GTAC' always blew my mind)

To be fair, this isn't the first time we've found such genes. Chronobiology (the study of the internal clocks of living things) has found a number of genes which directly influence our circadian rythyms, which causes all sorts of emergent behavior (changes in all the behavior which comes from your point in the cycle).

Immune wrote:

The moment you begin arguing that human behavior is innate, you might as well give up on democracy and free will.

Heh. Well, human behavior is the result of the interaction of genetics and the environment; our brain is designed such that it is very adept at altering itself according to the environment, and altering the environment to better suit it.

There is some evidence to suggest, however, that a huge portion of our genome has an impact on our intellect, though it wouldn't be surprising to learn that certain behaviors are to some extent genetic in nature.

Of course, there's a good chance free will is an illusion. We are, after all, very complicated meat machines.

Quote:

Incidentally, this should sound warning bells for anyone considering modifying genes in humans to "improve" humanity - behavioural changes resulting from such a thing could potentially eliminate what makes us "human."

Probably not. Not unless we severely impacted intelligence anyway. Making people smarter would probably make them more "human", if human indicates distance from animals.

Incidentally, this is pretty much a textbook example of the ideas Richard Dawkins put forth in his best (IMNSHO) book, "The Extended Phenotype" (which is basically a sequel, if you want to call it that, of "The Selfish Gene"). I highly recommend reading it if you want to get a good picture of this stuff (though, it is targeted more for biologists than the lay person, so it can be a tough read).

It is terribly easy to over-interpret this data. Let us start by admitting we do not know "why" one species builds a burrow that has a particular average shape. It could well be the mouse equivalent of taste.

Taste mapped pretty specifically to a small set of genetic traits that are different between the two related species, devoid of environmental cues or conditioning? Traits that are demonstrably heritable, and produce consistent behaviors when acted upon?

Quote:

Until proven, I do not believe that genes "code" for behaviors. Rather, behaviors emerge as a solution to certain drives.

I'm not sure what you think the overriding distinction is. If the mouse is burrowing a certain way because its genetic makeup predisposes it to feel "wrong" in a burrow that's too small or lacks an escape hatch, whether the cue it's acting upon is body odor or something else, how is that different? The genes are governing its behavior either way.

Quote:

Behavior does not reduce to base pairs despite the effort of some researchers to make it seem so.

This experiment is pretty compelling evidence that at least some behaviors do. And how else would you explain instinct, not just in these mice but also in other organisms like spiders, fish, birds, etc.?

To play devil's advocate a bit, consider an intelligent agent, with goals it must achieve and actions it can perform. In the highly unconstrained case, where it has a large number of actions that it can select with possibly very similar utilities, it might engage in a wide variety of behaviors over time. I don't think we would look at the sequence of actions the agent takes and say that they where encoded directly in the set of goals and possible actions that the agent possesses.

If we leave the agent the same but constrain its environment so that only a very small number of behaviors achieve its goals, to the point that it starts to repeat specific behaviors or patters of behavior consistently, I don't think it would make sense to then switch over and say that the agent's behavior is then encoded in its set of goals and selectable actions. If the agent only has a goal and a set of actions, but its environment is such that only very few specific sequences of actions will work, then I would say that we still haven't directly encoded that action sequence into the agent. I think that might the fine distinction that Immune was aiming for.

I'll admit to not having read the source article, and thus not knowing exactly what the authors claimed or how they hedged. But it strikes me that there is an assumption, at least in the interpretation of these results here, that shouldn't be made.

That assumption is that the more complex, or "higher," behavior is the later-evolving trait. Suppose, instead, that all the mice originally dug escape tunnels. But, for many of them, selective pressures dictated that the simpler burrow was actually closer to optimal. Would you then be surprised that a single genetic mutation would then control the difference between digging tunnels and not? That mutation would not have to construct the entire behavior of escape tunnel digging (which could be the result of many, many genes), it would just have to "knockout" that developmental pathway at any stage.

Humans are animals. What we should learn from this study is that much more of our human behavior is genetically directed than we like to think. Free will is not a black or white issue. For example, when a bird builds its nest, it instinctively picks a location with certain characteristics and builds a particular type of nest (genetically controlled) but free will allows it to pick out which of the acceptable locations and which particular bits of building material it will use.

Humans engage in more complex behaviors which makes it seem like we use free will more, but actually no, the underlying principles are the same for all animals, just different levels of complexity.

It is terribly easy to over-interpret this data. Let us start by admitting we do not know "why" one species builds a burrow that has a particular average shape. It could well be the mouse equivalent of taste. One mouse might be more sensitive to body odors and prefers more ventilation. The value as an escape hatch could be an incidental benefit that became selected. Until proven, I do not believe that genes "code" for behaviors. Rather, behaviors emerge as a solution to certain drives. Similarly the hype about alcoholism, homosexuality, or even artistry and intelligence far overplays the concept of genetic hardwiring. Behavior does not reduce to base pairs despite the effort of some researchers to make it seem so.A plausible explanation could be that building an escape hatch is the rational product of feeling at risk. Slightly raising stress hormone levels could lead to that perception by one species of mouse. This in turn could be the indirect effect of metabolic or nutritional factors that no one would consider primary behavioral genes.

I don't know why this post is being voted down. The study, while it does show a genetic basis for a behavior, does not show how many steps there are in the process between genotype and phenotype. We have no way of knowing at what point selective pressure is applied to allow the spread of a particular kind of gene in the oldfield mice that will eventually give rise to a change in burrowing behaviour.

It does seem mind boggling that seemingly complex behavior could be mapped to only one or 2 genes. One part of me wonders if this is a hint that a living organism is more than just what you can see and touch, that there is some metaphysical aspect to everything. Oh well, discussion for a different forum.

Scientifically it makes me wonder if those few genes regulate a group of other genes. For example, maybe there are a bunch of genes that regulate digging behavior, and so only a few are needed to regulate the genes controlling digging to adjust the length of digging?

What we have here is a pure correlation. Let's not get excited just because the word gene is used. I am reminded of a joke from my childhood (forgive the pre-animal consideration setting). A scientist trains a frog to jump when he claps his hands. He then proceeds to intervene by sequentially removing the frogs limbs (you can read: reversibly anesthetize). By the time the fourth is inactive, the frog no longer jumps. Scientist writes in log: Removed fourth limb, frog is deaf.

Here we have a measurable behavioral change that correlates perfectly with the intervention. The amount of knowledge gained? I leave that up to you.

I have 2 pet rabbits at home, we have had them since they were old enough to live safely without their mother. These 2 little guys do lots of things that natural wild rabbits would do but haven't had that teaching from their parents due to us taking them home and having them as pets.

Ive always wondered how they know how to do these things...It makes sense if there is some genetic form learning or guidance that helps them develop these base skills.Maybe more advanced things such as tool use and higher thought processes have to be learnt but the simple necessities are already ingrained.

It does seem mind boggling that seemingly complex behavior could be mapped to only one or 2 genes. One part of me wonders if this is a hint that a living organism is more than just what you can see and touch, that there is some metaphysical aspect to everything. Oh well, discussion for a different forum.

Actually, we know they aren't. Brain injuries disprove the notion of the soul.

Quote:

Scientifically it makes me wonder if those few genes regulate a group of other genes. For example, maybe there are a bunch of genes that regulate digging behavior, and so only a few are needed to regulate the genes controlling digging to adjust the length of digging?

Very likely it uses emergent complexity - the mouse probably has some sort of trigger for "how long is long enough", and some sort of other trigger that tells it that closed spaces are dangerous, so it makes it want to dig out that second tunnel as an escape route.

I would be unsurprised if these genes had some other impacts on behavior as well.